Study unpicks gene changes behind breast cancer

May 17, 2012|Reuters

* Research maps genetic codes of 21 breast cancers

* Helps scientists understand how disease evolves

* Raises hopes of earlier diagnosis and better treatment

By Kate Kelland

LONDON, May 17 (Reuters) - Scientists have mapped thecomplete genetic codes of 21 breast cancers and created acatalogue of the mutations that accumulate in breast cells,raising hopes that the disease may be able to be spotted earlierand treated more effectively in future.

The research, the first of its kind, untangles the genetichistory of how cancer evolves, allowing scientists to identifymutational patterns that fuel the growth of breast tumours, andstart to work out the processes behind them.

"These findings have implications for our understanding ofhow breast cancers develop over the decades before diagnosis inadults and might help to find possible targets for improveddiagnosis or therapeutic intervention in the future," said MikeStratton, who led the research team.

Breast cancer kills more than 450,000 women a year worldwideand is the most common cancer among women, accounting for 16percent of all cases, according to the World Health Organisation(WHO).

A study last year by the Institute for Health Metrics andEvaluation in the United States found that global breast cancercases have more than doubled in just three decades, from 641,000cases in 1980 to 1.6 million cases in 2010 - a pace that farexceeds global population growth.

"This is the first time we've been able to delve fully intobreast cancer genomes in such a thorough way," said PeterCampbell, head of cancer genetics and genomics at the WellcomeTrust Sanger Institute in Cambridge, where the studies were led.

The work had given scientists "a full panoramic view of thecancer genome" and helped them identify "mutational patternsrather than individual mutations in specific genes", he added.

DNA MUTATIONS

"We've known for many years now that all cancers are due toabnormalities of DNA...that occur in every single cell of thebody over the course of a lifetime," said Stratton.

"But although we've known that, it's remarkable howrudimentary our knowledge is about what the processes are thatcause these abnormalities, these mutations in our DNA."

Stratton's team sequenced the genomes of the 21 breastcancers and catalogued all the mutations. They found five majorprocesses that cause one letter of code to be changed to anotherletter. Genetic code comes in four DNA letters, A,C,G and T.

Stratton said one of the most exciting findings was that oneof these processes is characterised by small pockets ofmassively mutated regions of the genome.

This sudden "storm" of mutations is often seen in breastcancers, he explained in an audio briefing.

While his team don't fully understand the process behindthese storms, they think it may be down to components of thecell whose normal function is to edit, or mutate, DNA.

"What we believe...is that sometimes in normal cells...thisstops functioning properly and over-functions. It causes toomany mutations and the accumulation of those mutations pushesthe cell along the line to become cancer."

The team found that these and other mutations accumulate inbreast cells over many years, initially slowly, but picking upgreater momentum as genetic damage builds up.

By the time the breast cancers are large enough to bediagnosed, they are made up of a number of genetically relatedfamilies of cells, with one family dominating the cancer,Stratton explained.

Mark Walport, director of the Wellcome Trust which helpedfund the work, said the results showed how scientists arestarting to see the landscape of mutations in breast cancer "insomething approaching its full complexity".

"As this work continues, we can hope to understand howbreast cancer develops and thus how it might be treated moreeffectively," he said in a statement.